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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: adults
- Weight at study initiation: 3883 to 5461 g
- Housing: Individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5322, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20.5
- Humidity (%): 32 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
In one group the eyes of three rabbits were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing. In the other 3 animals, eyes were not rinsed.
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): In one group the eyes of three rabbits were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing. In the other 3 animals, eyes were not rinsed.
Left eyes were manipulated in an identical manner, including washing, if applicable, to simulate the dosing of the right eyes.

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: sodium fluorescein and ultraviolet light (72 h and 7 d)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
unwashed eyes
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
>= 2.33 - <= 3.33
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritation parameter:
iris score
Remarks:
unwashed eyes
Basis:
animal: 1 - 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritation parameter:
conjunctivae score
Remarks:
unwashed eyes
Basis:
animal: 1 - 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2.67
Max. score:
3
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritation parameter:
chemosis score
Remarks:
unwashed eyes
Basis:
animal: 1 - 3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks:
only 7 d observation; final evaluation of reversibility not possible
Irritant / corrosive response data:
The untreated left eyes of all rabbits were free of evidence of ocular irritation and other findings for the duration of the study.
All three ocular structures were affected by instillation of the test item. Findings included hemorrhages, blanching, corneal epithelia damage (peeling).
Irritation was less in the washed group. Also, some limited evidence of recovery was present in the washed group. Based on the data obtained, the test material is considered to cause irreversible effects to the eye.
Other effects:
There were no deaths during the study period. None of the rabbits vocalized upon instillation of the test material.
Slight body weight losses were observed for three rabbits. These losses were possibly stress-related due to the severe irritation observed. No other remarkable body weight changes were noted.

Any other information on results incl. tables

Eyes not rinsed after instillation of test item

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

1 h

3/2/4

1/1/1

2/2/2

3/3/3

3/3/3

24 h

2/2/4

1/1/2

1/2/1

4/4/4

3/3/3

48 h

2/2/3

1/1/2

1/3/1

4/4/4

3/3/3

72 h

3/3/3

2/1/2

1/3/1

4/4/4

3/3/3

4 d

3/3/3

2/2/2

1/3/2

4/4/4

3/2/2

7 d

3/4/4

2/2/2

2/3/2

4/3/4

1/1/3

Average 24h, 48h, 72h

2.33/2.33/3.33

1.33/1/2

1/2.67/1

4/4/4

3/3/3

Reversibility

No

No

No

No

No

 

Eyes rinsed 30 s after instillation of test item

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

1 h

2/2/1

1/1/2

2/2/1

3/2/1

2/2/3

24 h

2/2/2

1/2/1

1/2/2

4/4/4

3/3/3

48 h

3/3/2

1/1/1

3/3/3

4/4/4

3/3/3

72 h

3/3/2

1/2/0

3/3/2

4/4/3

2/3/1

4 d

3/3/2

2/2/0

3/3/3

4/4/4

2/3/3

7 d

3/3/2

1/2/0

3/3/3

3/4/4

1/3/3

Average 24h, 48h, 72h

2.67/2.67/2

1/1.67/0.67

2.33/2.67/2.33

4/4/3.67

2.67/3/2.33

Reversibility

No

No

No

No

No

 

Animal

 

Timepoint

 

1

unwashed

1 h

b,d,e(100%)

 

 

24 h

a, d

 

 

48 h

a, d, e(100%)

 

 

72 h

a, d, e(100%), r(100%)

 

 

4 d

a, d, e(100%)

 

 

7 d

a, e(100%), r(100%)

2

unwashed

1 h

a, e (90%)

 

 

24 h

a, d

 

 

48 h

a, c, e (90%)

 

 

72 h

a, c, e (90%), r(90%)

 

 

4 d

a, c, e (90%)

 

 

7 d

b, c, e(50%), k, r(50%)

3

unwashed

1 h

a, d, e(100%)

 

 

24 h

a, d

 

 

48 h

a, d, e(100%)

 

 

72 h

a, d, e(100%), r(100%)

 

 

4 d

a, c, d, e(100%)

 

 

7 d

a, c, d, e(100%), r(100%)

4

washed

1 h

b, c, e(50%)

 

 

24 h

a, d

 

 

48 h

a, e(100%)

 

 

72 h

a, c, e(85%), r(85%)

 

 

4 d

a, c, e(85%)

 

 

7 d

b, c, e(30%), k, r(30%)

5

washed

1 h

b, e(80%)

 

 

24 h

a, d

 

 

48 h

a, c, e(100%)

 

 

72 h

a, c, e(100%), r(100%), s

 

 

4 d

a, c, e(100%), s

 

 

7 d

b, c, e(100%), r(100%), s

6

washed

1 h

b, e (20%)

 

 

24 h

a, d

 

 

48 h

a, c, e(100%)

 

 

72 h

b, c, e(100%), r(100%)

 

 

4 d

b, c, e(100%)

 

 

7 d

b, c, e(35%), r(35%)

 

a = Purulent Discharge

b = Clear discharge

c = Petite hemorrhage

d = Blanching

e = Corneal epithelial damage, peeling (% of area)

k = Corneal neovascularization

r = Sodium fluorescein stain retention (% of area)

s = Blood present in anterior chamber

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In this study, Di-C12-18 alkyldimethyl ammonium chloride (100% a.i.) caused irreversible effects to the eyes.
Executive summary:

In a primary eye irritation study according to Environmental Protection Agency FIFRA (11/82) and TSCA (8/82) guidelines 0.1 mL of Di-C12-18 alkyldimethyl ammonium chloride (100% a.i.) was instilled into the conjunctival sac of the right eye of 6 female New Zealand White rabbits. In one group of three, the eyes were washed with 120 milliliters of lukewarm tap water commencing approximately 30 seconds after dosing; in the remaining three animals the eyes were not washed. The left eyes were manipulated in an identical manner, including washing, if applicable, to simulate the dosing of the right eyes. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

All three ocular structures were affected by instillation of the test item. Irritation was less in the washed group. Also, some limited evidence of recovery was present in the washed group. In the group without rinsing after instillation, corneal opacity scores ranged from 2 to 3. Iris scores up to 2 were observed. Corneal redness scores of 2-3 and chemosis scores of 3 – 4 were observed. The effects were not reversible within the observation period of 7 days. Additionally, effects like blanching, corneal epithelial damage, and fluorescein retention were observed.

Based on the data obtained, the test material is considered to cause irreversible effects to the eye.